DELETION of a single gene switches the sexual orientation of female mice, causing them to engage in sexual behaviour that is typical of males. Korean researchers found that deleting the appropriately named FucM gene, which encodes an enzyme called fucose mutarotase, causes masculinization of the mouse brain, so that female mice lacking the gene avoid the advances of males and try to mate with other females instead. The findings probably have little relavence to human sexual orientation, however.

FucM is one of a family of enzymes involved in rearranging the atoms in small sugar molecules called monosaccharrides. In 2007, Chankyu Park of the Korea Advanced Institute of Science and Technology and his colleagues reported that these rearrangements facilitate the incorporation of the monosaccharide fucose into cellular proteins. This process is one of numerous chemical modifications that are well known to regulate the function of proteins, but the biological significance of FucM function in mammals was until now unclear.

Park and his colleagues therefore created genetically engineered (“knock-out”) mice lacking the FucM gene. Apart from a slight reduction in body weight, the mice seemed perfectly healthy and were no different in appearance from their normal littermates. But the researchers noticed something unusual when they put the mutant females into mating cages with normal, sexually vigorous males. Typically, the stud will approach a female, touch her body and then sniff her anal-genital region. If the female is receptive, she will invite the male to mount her, by arching her back and raising her hind quarters. But the mutant females actively avoided the advances of the males, suggesting that deletion of the FucM gene had somehow interefered with their sexual and reproductive behaviour.

In mice, sexual behaviour is mediated largely by pheromones secreted in the urine. These chemicals carry sexual signals – they enable the animals to recognize, and motivate them to approach, members of the opposite sex. Normally, females prefer the smell of male urine and vice versa, but females lacking the FucM gene were found to prefer the urine of other females to that of males, spending more time sniffing it when simultaneously presented with both. Their sexual behaviour was similar to that of males, too: they not only rejected the advances of males, but also attempted to mount and mate with other females. Nevertheless, they remained fertile – most became pregnant when forced to mate with a sexually experienced male, and the way they subsequently behaved towards their offspring was no different from normal females.

When the researchers examined the brains of the mutant females, they observed a reduction in the number of dopamine-producing cells in the anteroventral periventricular nucleus (AVPv), a part of the hypothalamus which regulates the release of hormones required for ovulation. The AVPv is known to differ in size between males and females – it is between two to four times larger in females, and contains more cells. It is smaller in females missing the FucM gene, and thus closely resembles that of normal males. The researchers therefore hypothesized that deleting the gene causes changes in brain development that masculinize the brains of the females.

They also speculated that the observed changes occur because deleting the FucM gene perturbs the function of alpha-fetoprotein (AFP). AFP normally protects the female mouse brain from masculinization, by binding to and sequestering the hormone oestrogen during development, and its function is thought to be regulated by the addition and removal of fucose molecules. To test this prediction, the researchers analyzed expression levels of AFP in the mutant females, and the chemical composition of the protein circulating in their bloodstream. This revealed that AFP was present at normal levels, but that there was a significant reduction in the number of AFP molecules that had fucose attached to them.

Other researchers have shown that the neural circuits underlying male behaviours are likely to exist in the normal female mouse brain, and the reverse is probably true. It is also likely that the embryonic human brain has the capacity to differentiate along both the male and female pathways, depending upon exposure to sex hormones during the early stages of development.

These new findings show that FucM is critical for steering the developing mouse brain towards female diffrentiation. But they probably have limited relavence to human sexuality, because although FucM probably plays the same role in humans, oestrogen does not masculinize the developing human brain. There has been much talk of a “gay gene” in recent years, but no such gene has been discovered, It is, however, only a matter of time before the genes governing human sexual orientation are found.

Do the lesbian mice attempt to mount other lesbian mice, or only unaltered females? Is their hormone production more similar to that of a male or female mouse?

Also, RE: gay gene, I know we learned in psych 201, back in ’99, that there was solid evidence that sexual dimorphism in the human brain was caused by threshold testosterone levels, and that studies suggested a strong correlation between suppressed testosterone levels in mothers and homosexuality in their sons.

The study that stuck in my mind was one that showed that men were substantially more likely to be gay if their mother’s home city was bombed while they were in their second trimester. High levels of stress suppress testosterone production. As far as I know, being bombed does not correlate with any gene.

Disection of ‘gay brains’ also showed substantial difference in the development of the sexually dimorphic nucleus, and gays were also shown to produce characteristically female hormones (such as those associated with lactation.)

On the other hand, all of this is from memories of something that came up in a class I took more than a decade ago… Maybe it was discredited, or superceded by new research, but given the dominant ideologies of the last decade, I think it far more likely that it was simply ignored.

~nod, nod~ as well, nature versus nurture. Ultimately it really depends on what people think of variations… Designed – astray from purpose, or is genetic mutation (natural, as opposed to engineered) part of the many factors life hands over to individuals? I don’t know if I am stretching it if I invite you to apply the same logic with the physically and mentally challenged people.

Dear petrossa,

Lol, there was some genetic solution to make sterile bug of some sort I think (got to check parasitology notes on that one but regardless); as Corbier repeated, they were still fertile and

Yes, Corbier, it happens in nature all the time. I wonder if someone would complain if the female was physically bound though—wait no, now, does anyone care about the sexual act itself or the insemination? Because that is also a common practice in food industry/breeding …

I think that this finding has a lot relavence to human sexual orientation.
A long time ago we did not believe that a woman can be interested in a woman only or a man in a man only.
This finding can explain us a little.

Do you have citations for your assertion that progesterone masculinizes the fetal brain? I could have sworn that testosterone was responsible, e.g., as shown by XY cases of androgen insensitivity syndrome……

I think this would be much better titled “Researchers create ‘trans-gendered’ mice by deleting a single gene.” Masculanization of the brain is what caused the “lesbian” behavior. Trans-gendered would speak more truely to the mice being female but behaving as males. A male gendering is not what influences lesbian behavior in human females.

Agree with @17, sort of. The use of the word “lesbian” in the title is problematic (but so is the use of trans-gendered), not only for it’s anthropomorphism, but also because what the study is really exploring is the masculanization of female mice, which, even though it may cause females to mount other females, does not a lesbian make. I appreciate that you pointed out (several times) that no inferences can be made regarding human sexual behavior. I think you could have said it 100 more times and that wouldn’t have been too many! Perhaps I’m old and have lost my sense of humor (although I do love the word FUCK, perhaps a little more than is appropriate for a dowdy, middle-aged mother), but I think naming the enzyme FucM was a very unfortunate mistake (and possibly even misogynist). Is their similar research conducted on the feminization of male mice? And I can’t help wonder why “forced intercourse” was employed rather than artificial insemination? Perhaps it takes more time, energy, effort and money — but I, too, find it curious that this would be acceptable to any animal research review board (although given that rape in humans is socially sanctioned, I guess it shouldn’t be a surprise). It’s almost enough to make me want to take up arms with a violent, lesbian separatist, PETA group. Almost. Not quite. Oh, FUCK ‘EM.

What is also a bit of a surprise to me is that I didn’t see anyone mention what may be a real (and significant) implication of this study: that, given the right “equipment,” males make perfectly fine nurturers of the young.